Brugia malayi is a causative agent of human lymphatic filariasis (more commonly known as elephantiasis), a neglected tropical disease that is the second leading cause of morbidity worldwide. The mass drug administration programs currently in place for control and elimination have been successful in mitigating the prevalence of this painful, disfiguring, and incapacitating disease, but they are insufficient in reaching elimination by 2020, in particular in areas where loasis is co-endemic. The purpose of this project is to accelerate achievement of this goal. To that end, we intend to define the mechanisms of interdependency between the parasitic nematode B. malayi and its essential bacterial endosymbiont, Wolbachia, to identify new means of treatment that can irreversibly sterilize adult female worms or kill the adult worms. While B. malayi and its endosymbiont are known to be co-dependent, the basis of this relationship has yet to be elucidated. We know that using antibiotics to eliminate Wolbachia from the parasites affects development, reproduction, and survival of the adult worms in the host, indicating that the bacteria are crucial for the parasite, and therefore, represent an attractive target for curing the infection. We will focus on the interaction of the parasite and its endosymbiont at the molecular level using candidate Wolbachia-Brugia protein complexes and pathways that have been identified as essential players in the endosymbiotic relationship. Our three primary aims are: (1) to characterize the complexes Wolbachia surface proteins form with worm glycolytic enzymes and the cytoskeleton; (2) to define the physiological role of Wolbachia-Brugia protein complexes in worm development; and (3) to describe the essential functions provided by Wolbachia in the establishment of the filarial infection in the human host. Answering important questions about the endosymbiotic relationship will not only support the eradication of this disease but also yield groundbreaking information vital to future studies in the Wolbachia research field.